Bicyclic amidines, process for their preparation, and their use as catalyst

ABSTRACT

The process for the preparation of bicyclic amidines of the general formula: ##STR1## wherein A is selected from the group consisting of --CR 1  R 2  --CR 3  R 4  --CR 5  R 6  --, --CR 1  R 2  --CR 3  R 4  --CR 5  R 6  --CR 7  R 8  -- and --CR 1  R 2  --CR 3  R 4  --CR 5  R 6  --CR 7  R 8  --CR 9  R 10  --, wherein the substituents in A are in each case numbered starting from the nitrogen atom, and B is selected from the group consisting of --CR 11  R 12  --CR 13  R 14  --, --CR 11  R 12  --CR 15  R 16  --CR 13  R 14  -- and --CR 11  R 12  --CR 15  R 16  --CR 17  R 18  --CR 13  R 14  --, and R 1 , R 2  and R 11  to R 14  are, in each case independently of one another, hydrogen, C 1  -C 4  -alkyl, aryl, or are C 1  -C 4  -alkyl which is substituted with hydroxyl, amino, C 1  -C 4  -alkylamino or mercapto, and R 3  to R 10  and R 15  to R 18  are, in each case independently of one another, hydrogen, C 1  -C 4  -alkyl, aryl, hydroxyl, amino, C 1  -C 4  -alkylamino or mercapto, or are C 1  -C 4  -alkyl which is substituted with hydroxyl, amino, C 1  -C 4  -alkylamino or mercapto. The process includes heating (reacting) a lactone of the general formula: ##STR2## wherein A is as defined above, to at least 150° C. together with an at least equimolar quantity of an amine of the general formula: 
     
         H.sub.2 N--B--NH.sub.2                                     III 
    
     wherein B is as defined above. The resultant reaction mixture is subjected, without isolating an intermediate, to a fractional distillation.

This is a continuation application of Ser. No. 08/339,191, filed on Nov.10, 1994, now U.S. Pat. No. 5,723,605.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to a novel process for the preparation of bicyclicamidines by reaction of lactones with primary amines. The invention alsorelates to novel bicyclic amidines having functional groups, especiallyamino, hydroxyl and/or mercapto groups, and to their use as catalystsfor the preparation of polyurethanes.

2. Background Art

Bicyclic amidines are strong organic bases which, owing to their highbasicity coupled with low nucleophilicity and their ready solubility inalmost all solvents, have found numerous applications. Particularlywell-known bicyclic amidine compounds are those commonly referred to bythe abbreviations DBN and DBU, i.e., 1,5-diazabicyclo 4.3.0!non-5-ene(2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine) and 1,8-diazabicyclo5.4.0! undec-7-ene(2,3,4,6,7,8,9,10-octahydropyrimido 1,2-a!azepine),respectively.

A review of the uses of these compounds in chemical syntheses can befound, for example, in Synthetica Merck, Volume II, E. Merck, Darmstadt,(1974), pp. 118-119 and 124.

A known process for preparing bicyclic amidines starts fromN-(ω-aminoalkyl)lactones which, when heated with acidic catalysts,undergo cyclization with elimination of water to form the amidines(German Patent No. C 1,545,855). The N-(ω-aminoalkyl)lactones areobtained, for example, from the corresponding cyano compounds byhydrogenation; in particular, for example, N-(γ-aminopropyl)pyrrolidoneis obtained from N-(β-cyanoethyl)-pyrrolidone see, e.g., W. Reppe etal., Justus Liebigs Ann. Chem., 596, (1955), p.211!. It is also possibleto prepare N-(ω-aminoalkyl)lactones from the corresponding lactones andα,ω-diaminoalkanes (German Patent No. C 730,182). The known processesfor the preparation of bicyclic amidines have the disadvantage that theyinclude at least two synthesis steps with working up of theintermediates.

It is known that bicyclic amidines are highly suitable as catalysts forthe preparation of polyurethanes (French Patent No. 1,542,058). Aconsiderable disadvantage of this use, however, is that bicyclicamidines are not firmly bonded within the polyurethane formed andtherefore, over time, diffuse out of or are extracted from thepolyurethane. In each case there is unnecessary pollution of theenvironment.

BROAD DESCRIPTION OF THE INVENTION

The main object of the invention is to provide an improved andsimplified process for the preparation of bicyclic amidines and, fromthis class of compounds, to provide new compounds which, when used ascatalyst for the preparation of polyurethanes, are bonded so firmly tothe polymer that they no longer have any notable tendency towardsmigration. Other objects and advantages of the invention are set outherein or obvious to one skilled in the art.

The objects and advantages of the invention are achieved by thepreparation process of the invention, the novel compounds of theinvention and the process of using the novel invention compounds.

The invention preparation process involves preparing bicyclic amidinesof the general formula: ##STR3## wherein A and B are defined below, in aone-pot process, without isolation or purification of intermediates,from the corresponding lactones of the general formula: ##STR4## whereinA is defined below, and amines of the general formula:

    H.sub.2 N--B--NH.sub.2                                     III

wherein B is defined below.

The group A in the lactone (II) and in the amidine (I) is in each case a3-, 4- or 5-membered carbon chain of the formula --CR¹ R² --CR³ R⁴ --CR⁵R⁶ --, --CR¹ R² --CR³ R⁴ --CR⁵ R⁶ --CR⁷ R⁸ -- or --CR¹ R² --CR³ R⁴ --CR⁵R⁶ --CR⁷ R⁸ --CR⁹ R¹⁰ --, where R¹ and R² are in each case attached tothe carbon atom which is adjacent to the heteratom.

The group B in the amine (III) and in the amidine (I) is in each case a2-, 3- or 4-membered carbon chain of the formula --CR¹¹ R¹² --CR¹³ R¹⁴--, --CR¹¹ R¹² --CR¹⁵ R¹⁶ --CR¹³ R¹⁴ -- or --CR¹¹ R¹² --CR¹⁵ R¹⁶ --CR¹⁷R¹⁸ --CR¹³ R¹⁴ --.

The general formula I, therefore, encompasses bicyclic amidines having5-, 6- or 7-membered rings; the two rings can have identical ordifferent numbers of members. Correspondingly, the general formula IIencompasses lactones having from 5 to 7 ring members, in other words,γ-, δ- and ε-lactones.

The substituents R¹, R², and R¹¹ to R¹⁴ of the carbon chains A and Bare, in each case independently of one another, hydrogen, C₁ -C₄ -alkylor aryl or C¹ -C₄ -alkyl groups which are in turn substituted withhydroxyl, amino, C₁ -C₄ -alkylamino or mercapto. The substituents R³ toR¹⁰ and R¹⁵ to R¹⁸ can be either the groups mentioned for R¹, R² and R¹¹to R¹⁴ or else hydroxyl, amino, C₁ -C₄ -alkylamino or mercapto groups.

C₁ -C₄ -alkyl here refers to all primary, secondary and tertiary,unbranched or branched alkyl groups having up to 4 carbon atoms, forexample, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl,and tert-butyl. Aryl refers in particular to phenyl or toalkyl-substituted phenyl, such as, o-, m- or p-tolyl or the variousisomeric xylyl groups. Examples of suitable lactones areγ-butyrolactone, γ- and δ-valero-lactone, ε-caprolactone or substitutedlactones such as pantolactone (2-hydroxy-3,3-dimethyl-γ-butyrolactone).

Functional groups as substituents, that is, hydroxyl, amino, alkylaminoor mercapto, are preferably located on the groups B of the aminecomponent (III).

Amines (III) which are suitable are therefore not only primary diaminesbut also compounds having additional primary or secondary amino groups.Examples of suitable amines are 1,2-diaminoethane, 1,2-diaminopropane,1,3-diaminopropane, 1,2,3-triaminopropane, 1,1,1-tris(aminomethyl)ethaneor tetrakis (aminomethyl)-methane. If amines having non-equivalent aminogroups are employed, then under some circumstances mixtures of productscan be formed--as in the case, for example, with 1,2-diaminopropane or1,2,3-triaminopropane.

When reacting the lactone (II) with the amine (III) it is advantageousto use a molar ratio of at least 1 mol of amine to 1 mol of lactone(i.e., 1 to 30 mols per mol). Preferably, from 2 to 20 mols of amine areemployed per mole of lactone. The excess of amine can be recovered whenworking up the reaction mixture.

The reaction is advantageously carried out at a temperature of at least150° C. The reaction temperature is preferably between 200° and 300° C.The addition of an inert solvent, such as, toluene or xylene, whilepossible, is not necessary. The reaction is preferably carried outwithout solvent. In order to attain the reaction temperature it isgenerally necessary to maintain the reaction mixture under elevatedpressure, since the boiling points of many starting materials atatmospheric pressure are lower than the reaction temperature. In orderto achieve this, customary autoclaves can be employed. In order toaccelerate the reaction it is preferable to add an acidic catalyst.Suitable catalysts are Br.o slashed.nsted acids, such as, hydrochloricacid, sulfuric acid, phosphoric acid or ammonium chloride, oralternatively acidic aluminium silicates or acidic metal oxides, suchas, tin (IV) oxide or antimony (III) oxide.

In accordance with the invention, the reaction mixture is distilleddirectly without isolating an intermediate. For practical reasons, thisis typically carried out by transferring the reaction mixture from theautoclave to a distillation apparatus. If appropriately equippedapparatus suitable both for superatmospheric pressure and reducedpressure is available, the reaction of the lactone with the amine andthe distillation can be carried out in one and the same apparatus. Inthe distillation, the initial fraction passing over is the water formedduring cyclization and the excess amine, followed by the amidine.Depending on the boiling point of the product, the distillation iscarried out at an appropriately reduced pressure.

Using the process according to the invention, the known bicyclicamidines mentioned in the background section, such as, DBN and DBU, butalso, in particular, novel compounds from this class of substances,having previously unobtained properties, can be prepared.

It has been found that those bicyclic amidines (I) in which at least oneof the substituents R¹ to R¹⁸ is and/or carries a primary or secondaryamino group, a hydroxyl group and/or a mercapto group can be used ascatalyst for the preparation of polyurethanes and are bonded so firmlywithin the polymer that no migration can be detected either during useor in the course of the customary extraction tests. It is presumed that,during the preparation of the polyurethane, these additional functionalgroups react with the isocyanate groups of the isocyanate component ofthe polyurethane and form covalent bonds.

The additional functional groups can of course also be used for otherorganic reactions with polymeric or nonpolymeric isocyanates, epoxides,carboxylic acids, carboxylic acid derivatives or other compounds.

The additional functional groups are preferably amino groups oraminoalkyl groups, such as, aminomethyl groups. They are preferablylocated on the chain which in the general formula is designated "B", inother words in the positions of substituents R¹¹ to R¹⁸.

The compounds which are particularly preferred are3-amino-2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine: ##STR5##3-(aminomethyl)-2,5,6,7-tetrahydro-3H-pyrrolo 1,2-a!imidazole: ##STR6##both individually and as a mixture,

and 3-(aminomethyl)-3-methyl-2,3,4,6,7,8-hexahydropyrrolo1,2-a!pyrimidine: ##STR7##

DETAILED DESCRIPTION OF THE INVENTION

The examples which follow will illustrate the implementation of theprocess according to the invention and the properties and uses of thecompounds according to the invention.

EXAMPLE 1 Preparation of 2,5,6,7-tetrahydro-3H-pyrrolo 1,2-a!imidazole(1,4-diazabicyclo 3.3.0!oct-4-ene)

A mixture of 129 g (1.5 mol) of γ-butyrolactone, 8 g (0.15 mol) ofammonium chloride and 360 g (6 mol) of 1,2-diaminoethane was heated at250° C. in an autoclave. After 2.5 h, the mixture was cooled and theexcess diaminoethane and the water formed were removed by distillation.The residue was distilled at 200° C./200 mbar. By heating the distillatein vacuo, the residual water was removed. The yield was 125 g (76%) ofcolorless oil which gradually solidifies to form a wax-like mass.

EXAMPLE 2 Preparation of 3-amino-2,3,4,6,7,8-hexahydropyrrolo-1,2-a!-pyrimidine and 3-(aminomethyl)-2,5,6,7-tetrahydro-3H-pyrrolo-1,2-a!imidazole

21.52 g (0.25 mol) of γ-butyrolactone, 1.34 g (25 mmol) of ammoniumchloride and 83.43 g (0.94 mol) of 1,2,3-triaminopropane were reactedanalogously to Example 1. The residue which remained after distillativeremoval of the excess amine and of the water was distilled at 170° to200° C. (bath temperature)/0.1 mbar. The yield was 22.2 g (64%) ofyellowish oil. The boiling point was 95°-97° C./2 mbar.

According to GC, the product consisted of about 90 percent of the isomerhaving the pyrrolo 1,2-a!pyrimidine structure and about 10 percent ofthe isomer having the pyrrolo 1,2-a!imidazole structure:

3-Amino-2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine

¹ H-NMR (CDCl₃, 400 MHz) δ: 1.96 (quint, 2H, H-7); 2.45 (t, 2H, H-8);2.7-2.8 (m, 1H, H-4_(a)); 3.05 (t, 1H, H-2_(a)); 3.1-3.2 (m, 1H, H-3);3.3 (t, 2H, H-6); 3.35 (t, 1H, H-4_(b)); 3.45-3.5 (m, 1H, H-2_(b)).

¹³ C-NMR (100 MHz) δ: 160.5 (s, C-8a); 52.88 (t, C-2); 51.4 (t, C-6);50.9 (t, C-4); 43.0 (t, C-3); 30.9 (t, C-8); 20.0 (t, C-7).

3-(Aminomethyl)-2,5,6,7-tetrahydro-3H-pyrrolo 1,2-a!-imidazole

¹ H-NMR (CDCl₃, 400 MHz) δ: 2.28-2.32 (m, 2H, H-6); 2.32-2.35 (m, 2H,H-7); 2.75 (m, 1H, CH_(a) NH₂); 2.85 (m, 2H, H-5); 3.3 (m, 1H, CH_(b)NH₂); 3.4 (m, 1H, H-3); 3.8 (dd, 1H, H-2_(a)); 4.15 (dd, 1H, H-2_(b)).

¹³ C-NMR (CDCl₃, 100 MHz) δ: 175.8 (s, C-7a); 64.5 (t, C-2); 64.3 (d,C-3); 45.8 (t, CH₂ NH₂); 44.3 (t, C-5); 25.4 (t, C-7); 22.6 (t, C-6).

EXAMPLE 3 Preparation of3-(aminomethyl)-3-methyl-2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine

A mixture of 21.03 g (0.24 mol) of γ-butyrolactone and 1.31 g (24 mmol)of ammonium chloride in 114.5 g (0.98 mol) of1,1,1-tris(aminomethyl)ethane was heated at 250° C. in an autoclave.After 1.5 h, the mixture was cooled and the excess amine and the waterformed were removed by distillation. The residue was distilled at200°-240° C./18 mbar. The yield was 22.0 g (54%) of yellowish oil. Theboiling point was 117°-120° C./1 mbar. Other data concerning the productwas:

¹ H-NMR (CDCl₃, 400 MHz) δ: 0.91 (s, 3H, CH₃); 1.95 (quint, 2H, H-7);2.45 (t, 2H, H-8); 2.53 (dd, 2H, CH₂ NH₂); 2.84 (dd, 1H, H-4_(a)); 3.0(m, 2H, H-2_(a), H-4_(b)); 3.13 (dd, 1H, H-2_(b)); 3.28 (dt, 2H, H-6).

¹³ C-NMR (CDCl₃, 100 MHz) δ: 160.1 (s, C-8a); 53.5 (t, C-2); 51.5 (t,C-6); 51.3 (t, C-4); 48.5 (t, CH₂ NH₂); 32.0 (s, C-3); 30.9 (t, C-8);20.9 (q, CH₃) 19.9 (t, C-7).

EXAMPLE 4 Preparation of 2,5,6,7-tetrahydro-3H-pyrrolo 1,2-a!-imidazole

A mixture of 86 g (1 mol) of γ-butyrolactone and 2 ml of 98 percentstrength sulfuric acid in 240 g (4 mol) of 1,2-diaminoethane was heatedat 250° C. in an autoclave. After 4.5 h, the reaction mixture was cooledand worked up as described in Example 1. The yield was 90 g (82%). Forproperties of the product, see Example 1.

EXAMPLE 5 Preparation of 2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine(1,5-diazabicyclo 4.3.0!non-5-ene, DBN)

A mixture of 43 g (0.5 mol) of γ-butyrolactone and 2.68 g (25 mmol) ofammonium chloride in 148 g (2 mol) of 1,3-diaminopropane was heated at250° C. in an autoclave. After 4.5 h, the mixture was cooled and theexcess amine and the water formed were removed by distillation up to 250mbar. The residue was distilled in vacuo. The yield was 47 g (75%) ofcolorless liquid. The boiling point was 98° C./12 mbar.

EXAMPLE 6 Preparation of 2,3,4,6,7,8,9,10-octahydropyrimido1,2-a!azepine (1,8-diazabicyclo 5.4.0!undec-7-ene, DBU)

The procedure described in Example 5 was followed with the differencethat, instead of γ-butyrolactone, 57 g (0.5 mol) of ε-caprolactone wasemployed. The yield was 16 g (21%) of colorless liquid. The boilingpoint was 115° C./8 mbar.

EXAMPLES 7 TO 9 Preparation of polyurethanes using bicyclic amidines ascatalyst

General Procedure:

At room temperature 50 g of an aromatic polyisocyanate based ondiphenylmethane diisocyanate (about 32 percent of NCO) was added, whilestirring with a glass rod, to a solution of 0.5 g of the amidine in 55 gof a trifunctional, hydroxyl-containing branched polyether (Desmophen®550 U, about 11.5 percent of OH). A film about 200 μm thick was castfrom each mixture. After curing had been carried out, the migrationcapacity of the amidine was determined by extraction testing. For thispurpose, 10 g of each of the films thus obtained, cut into small pieces,were stored in 40 ml of methanol at room temperature. After variousintervals, the amidine content in samples of the methanol was determinedby GC.

EXAMPLE 7 (COMPARISON EXAMPLE)

The amidine employed was 2,3,4,6,7,8-hexahydropyrrolo- 1,2-a!pyrimidine(DBN). The gel time was 3 mins., 15 s. The amidine content in theextraction test was:

    ______________________________________    after 1 h           about 0.012%    after 1 day         about 0.06%    after 14 days       about 0.1%    ______________________________________

After 14 days, therefore, the majority of the total amount of amidinepresent had been extracted.

EXAMPLE 8

The amidine employed was a mixture of about 90 percent of3-amino-2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine and about 10percent of 3-(aminomethyl)-2,5,6,7-tetrahydro-3H-pyrrolo 1,2-a!imidazole(prepared according to Example 2). The gel time was 3 mins, 30 s. Theamidine content was:

    ______________________________________           after 1 h     <10 ppm           after 1 day   <10 ppm           after 14 days <10 ppm    ______________________________________

EXAMPLE 9

The amidine employed was3-(aminomethyl)-3-methyl-2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine(prepared according to Example 3). The gel time was 3 mins. The amidinecontent was:

    ______________________________________           after 1 h     <10 ppm           after 1 day   <10 ppm           after 14 days <10 ppm    ______________________________________

In the case of the amidines, according to the invention, the extractedquantity, even after 14 days, was still below the detection limit.

EXAMPLES 10 TO 12

General procedure:

At room temperature, 40 g of an aliphatic triisocyanate (about 23percent of NCO) was added, while stirring with a glass rod, to asolution of 0.44 g of the amidine and 30 mg of dibutyl tin dilaurate ina mixture comprising in each case 24 g of a trifunctional,hydroxyl-containing branched polyether (Desmophen® 550 U, about 11.5percent of OH and Desmophen® 1915 U, about 1.1 percent of OH). A filmabout 200 μm thick was cast from the mixture and the procedure ofExamples 7 to 9 was then followed.

EXAMPLE 10 (COMPARISON EXAMPLE)

The amidine employed was 2,3,4,6,7,8-hexahydropyrrolo 1,2-a! pyrimidine(DBN). The gel time was 70 s. The amidine content in the extraction testwas:

    ______________________________________    after 1 day           <10 ppm    after 14 days         <10 ppm    after 2 months        0.03%    ______________________________________

EXAMPLE 11

The amidine employed was a mixture of about 90 percent of3-amino-2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine and about 10percent of 3-(aminomethyl)-2,5,6,7-tetrahydro-3H-pyrrolo1,2-a!-imidazole (prepared according to Example 2). The gel time was 75s. The amidine content was:

    ______________________________________    after 1 h             <10 ppm    after 14 days         <10 ppm    after 2 months        <10 ppm    ______________________________________

EXAMPLE 12

The amidine employed was3-(aminomethyl)-3-methyl-2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine(prepared according to Example 3). The gel time was 65 s. The amidinecontent was:

    ______________________________________    after 1 h             <10 ppm    after 1 day           <10 ppm    after 2 months        <10 ppm    ______________________________________

Examples 10 to 12 also exhibit, after a long period of testing (2months), a considerable reduction in the tendency towards migration.

What is claimed is:
 1. A bicyclic amidine of the formula: ##STR8##wherein CR¹ R² of A is --CR¹ R² --CR³ R⁴ --CR⁵ R⁶ --, wherein A isattached to the nitrogen atom, and B is --CR¹¹ R¹² --CR¹⁵ R¹⁶ --CR¹³ R¹⁴--, wherein CR¹¹ R¹² of B is attached to the nitrogen atom having adouble bond, and R¹, R² and R¹¹ to R¹⁴ are, in each case independentlyof on another, hydrogen, C₁₋₄ -alkyl, aryl, or are C₁₋₄ -alkyl which issubstituted with hydroxyl, primary amino, mono-C₁₋₄ -alkylamino ormercapto, and R³ to R⁶, R¹⁵ and R¹⁶ are, in each case independently ofone another, hydrogen, C₁₋₄ -alkyl, aryl, hydroxyl, primary amino,mono-C₁₋₄ -alkylamino or mercapto, or are C₁₋₄ -alkyl which issubstituted with hydroxyl, primary amino, mono-C₁₋₄ -alkylamino ormercapto, with at least one of the substituents R¹¹ to R¹⁶ being aminoor aminomethyl, with the proviso that at least one of the substituentsR¹ to R⁶ and R¹¹ to R¹⁶ is hydroxyl, primary amino, mono-C₁₋₄-alkylamino, mercapto or C₁₋₄ -alkyl substituted with at least onemember selected from the group consisting of hydroxyl, primary amino,mono-C₁₋₄ -alkylamino and mercapto, with the proviso that, if R¹ or R²is C₁₋₄ -alkyl which is substituted with primary amino, the remaining ofR¹ and R² is hydrogen, and with the proviso that, if R⁵ or R⁶ is amember selected from the group consisting of mercapto, aminomethyl andmethylamino, the remaining of R⁵ and R⁶ is not methyl. 2.3-Amino-2,3,4,6,7,8-hexahydropyrrolo 1,2-a!pyrimidine of the formula:##STR9##
 3. 3-(Aminomethyl)-3-methyl-2,3,4,6,7,8-hexahydopyrrolo-1,2-a!pyrimidine of the formula: